Kidney Injury in Patients with Acute Decompensated Heart Failure

摘要 急性失代偿性心力衰竭（ADHF）的住院治疗是一个重要的公共卫生问题， 是一个前哨预后事件，在治疗期间和治疗后临床结局不良的风险很高。 住院调查以改善对ADHF患者的护理是公共卫生的优先事项。肾脏 在ADHF的急性管理和预后中发挥核心作用。肾损伤是非常普遍的， ADHF是血流动力学改变、神经激素失调和氧化应激的结果 其引起肾内内皮损伤、炎症和缺血性损伤。肾损伤也是一个关键 决定开始和退出标准AHDF治疗的组成部分，最终影响 ADHF的临床预后。然而，对肾损伤的系统测量和考虑并不 纳入ADHF治疗算法，可能是由于目前临床可用肾脏的局限性 伤害措施。传统上，血清肌酐用于定义ADHF中的肾损伤， 是晚期的，并且响应于正在进行的肾损伤或修复而缓慢改变;这限制了其在动态治疗中的应用。 如ADHF。研究表明，血清肌酐与全身性 缓解充血或与ADHF的短期预后有关。因此，目前的ADHF指南不支持连续 血清肌酐的测量。这项提案的目的是确定新的肾损伤标志物， 指导治疗并更好地确定ADHF的预后;从而改善住院和长期结局。 为了解决这一知识缺口，我们建议对ADHF患者进行一项大型前瞻性研究， 确定：（1）新的肾损伤标志物的系统性、连续测量是否响应于一种新的治疗而改变。 标准化的、循证的ADHF治疗方案;（2）这些变化是否与 患者报告、住院和长期结局。根据以往的文献，我们选择了研究一个 一组新的肾损伤指标，包括内皮损伤、炎症、肾小管应力/损伤， 更好地反映了肾内病理生理学，并且可能更动态地反映肾损伤/修复， 血清肌酐这些新的肾损伤措施有望在近期临床上得到应用。 然而，在ADHF中没有很好地研究。为了支持我们的假设，我们进行了一项前瞻性的试点研究， 对62例ADHF患者的研究发现，新的肾损伤指标显示， 标准化ADHF治疗的相对变化与全身充血相关; 而血清肌酐相对稳定，与全身充血相关性差。这 有希望的试点数据支持拟议工作的科学依据和可行性。数据 本研究的结果将用于确定ADHF患者中最有希望的肾损伤标志物， 未来机制研究或临床试验的基础，以测试ADHF治疗策略， 新的肾损伤标记物。

ABSTRACT Hospitalization for acute decompensated heart failure (ADHF) is a significant public health issue and represents a sentinel prognostic event, with high risk of poor clinical outcomes during and after the hospitalization. Investigation to improve the care of ADHF patients is a public health priority. The kidneys have a central role in the acute management and prognosis of ADHF. Kidney injury is highly prevalent in ADHF and is the culmination of hemodynamic alterations, neurohormonal dysregulation, and oxidative stress which cause intra-kidney endothelial damage, inflammation and ischemic injury. Kidney injury is also a key component in decisions of initiation and withdrawal of standard AHDF therapies, which ultimately affects clinical prognosis of ADHF. However, systematic measurement and consideration of kidney injury is not incorporated into algorithms of ADHF therapies, likely due to limitations of current clinically available kidney injury measures. Serum creatinine has traditionally been used to define kidney injury in ADHF, however rises late and is slow to change in response to ongoing kidney injury or repair; which limits its use in dynamic conditions such as ADHF. Studies have shown that serum creatinine is not associated with systemic decongestion or with short-term prognosis in ADHF. Thus, current ADHF guidelines do not endorse serial measures of serum creatinine. The goal of this proposal is to identify novel kidney injury markers that can guide therapy and better determine prognosis in ADHF; thereby improve in-hospital and long-term outcomes. To address this knowledge gap, we propose to conduct a large, prospective study of ADHF patients to determine: (1) if systematic, serial measurements of novel kidney injury markers change in response to a standardized, evidence-based ADHF treatment protocol; (2) and whether these changes are associated with patient-reported, in-hospital and long-term outcomes. Based on previous literature, we have chosen to study a panel of novel kidney injury measures of endothelial injury, inflammation, tubular stress/damage which may better reflect intra-kidney pathophysiology, and may be more dynamic to reflect kidney injury/repair compared with serum creatinine. These novel kidney injury measures are poised to be clinically available in the near future, however are not well studied in ADHF. To support our hypothesis, we conducted a pilot prospective study of 62 patients admitted with ADHF and found that novel kidney injury measures demonstrated greater relative change in response to standardized ADHF therapies and correlated well with systemic congestion; while serum creatinine was relatively static and correlated poorly with systemic congestion. This promising pilot data supports the scientific rationale and feasibility of the proposed work. The data from this study will be used to identify the most promising kidney injury markers in ADHF patients and may be the foundation of future mechanistic studies or a clinical trial to test an ADHF treatment strategy guided by novel kidney injury markers.